Role of 5-HT2C receptors of the dorsal hippocampus in the modulation of anxiety- and panic-related defensive responses in rats.

Autor: Sant'Ana AB; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Vilela-Costa HH; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Vicente MA; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., Hernandes PM; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil., de Andrade TGCS; Department of Biological Science, São Paulo State University (UNESP), Assis, SP, Brazil., Zangrossi H Jr; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, Brazil. Electronic address: zangross@fmrp.usp.br.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2019 Apr; Vol. 148, pp. 311-319. Date of Electronic Publication: 2019 Jan 25.
DOI: 10.1016/j.neuropharm.2019.01.026
Abstrakt: The role of 5-HT2C receptors (5-HT2CRs) in the regulation of anxiety has been widely acknowledged. However, conflicting results have been reported on whether stimulation of these receptors increases or decreases anxiety. We here investigated the role of 5-HT2CRs of the dorsal hippocampus (DH) in the mediation of anxiety- or panic-associated defensive behaviors and in the anxiolytic effect of the tricyclic antidepressant imipramine. In the Vogel conflict test, administration of the mixed 5-HT2CR agonist mCPP into the DH of male Wistar rats was anxiogenic, whereas infusions of the more selective agonists MK-212 and RO-600175 were anxiolytic. The 5-HT2CR antagonist SB-242084, on the other hand, was anxiogenic. A sub-effective dose of this antagonist blocked the anxiolytic effect of RO-600175, but not the increase in anxiety observed with mCPP, indicating that the latter effect was not due to 5-HT2CR activation. In full agreement with these findings, MK-212 and RO-600175 in the DH also inhibited inhibitory avoidance acquisition in the elevated T-maze, whereas SB-242084 caused the opposite effect. None of these drugs interfered with escape expression in this test, which has been associated with panic. Chronic administration of imipramine (15 mg/kg, ip, 21 days) caused an anxiolytic effect in the elevated T-maze and light-dark transition tests, which was not blocked by previous infusion of SB-242084 into the DH. Therefore, facilitation of 5-HT2CR-mediated neurotransmission in the DH decreases the expression of anxiety-, but not panic-related defensive behaviors. This mechanism, however, is not involved in the anxiolytic effect caused by imipramine.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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